Subtotal resection of vestibular schwannoma: evaluation with Ki-67 measurement, magnetic resonance imaging, and long-term observation

Purpose The aim of this study was to compare the postoperative clinical and radiological data of patients with vestibular schwannomas who were initially managed by near total resection (NTR) or subtotal resection (STR). The Ki-67 analysis results were compared with tumor regrowth to determine the presence of a correlation between this proliferative index and postoperative tumor regrowth. Study Design Seventeen adult patients (7 male, 10 female) were retrospectively reviewed. Nine (52.9%) and eight (47.1%) patients underwent NTR and STR, respectively. Postoperative clinical and radiological data associated with vestibular schwannoma growth were compared with the Ki-67 immunohistochemical analysis results. Results Evidence of clinically significant regrowth was observed in four (23.5%) patients. Patients who underwent NTR had a lower rate/incidence of tumor regrowth than did patients who underwent STR. Patients with a higher Ki-67 index had the highest tumor regrowth rates. Conclusions Our study indicates that assessment of the Ki-67 index may be useful for determining the probability of regrowth of vestibular schwannomas when only partial removal is accomplished

Altered Ca 2+ concentration, permeability and buffering in the myofibre Ca 2+ store of a mouse model of malignant hyperthermia: Ca2+management in Y522S cells

Malignant hyperthermia (MH) is linked to mutations in the type 1 ryanodine receptor, RyR1, the Ca2+ channel of the sarcoplasmic reticulum (SR) of skeletal muscle. The Y522S MH mutation was studied for its complex presentation, which includes structurally and functionally altered cell ‘cores’. Imaging cytosolic and intra-SR [Ca2+] in muscle cells of heterozygous YS mice we determined Ca2+ release flux activated by clamp depolarization, permeability (P) of the SR membrane (ratio of flux and [Ca2+] gradient) and SR Ca2+ buffering power (B). In YS cells resting [Ca2+]SR was 45% of the value in normal littermates (WT). P was more than doubled, so that initial flux was normal. Measuring [Ca2+]SR(t) revealed dynamic changes in B(t). The alterations were similar to those caused by cytosolic BAPTA, which promotes release by hampering Ca2+-dependent inactivation (CDI). The [Ca2+] transients showed abnormal ‘breaks’, decaying phases after an initial rise, traced to a collapse in flux and P. Similar breaks occurred in WT myofibres with calsequestrin reduced by siRNA; calsequestrin content, however, was normal in YS muscle. Thus, the Y522S mutation causes greater openness of the RyR1, lowers resting [Ca2+]SR and alters SR Ca2+ buffering in a way that copies the functional instability observed upon reduction of calsequestrin content. The similarities with the effects of BAPTA suggest that the mutation, occurring near the cytosolic vestibule of the channel, reduces CDI as one of its primary effects. The unstable SR buffering, mimicked by silencing of calsequestrin, may help precipitate the loss of Ca2+ control that defines a fulminant MH event

Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies

As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (\ub12) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS-CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies

BNT162B2 mRNA COVID-19 vaccine in heart and lung transplanted young adults: is an alternative SARS-CoV-2 immune response surveillance needed?

[no abstract available

Perinatally Human Immunodeficiency Virus-Infected Adolescents and Young Adults Demonstrate Distinct BNT162b2 Messenger RNA Coronavirus Disease 2019 Vaccine Immunogenicity<SUP> </SUP>

BackgroundImmunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability, and efficacy.MethodsSafety and immunogenicity profiles of BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine, among people living with human immunodeficiency virus (HIV), were evaluated in 28 perinatally HIV-infected patients under antiretroviral therapy (ART) and 65 healthy controls (HCs) with no previous history of COVID-19. Thus, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and CD4+ T cell responses. Samples were collected before vaccination (baseline, day [D] 0), at the second dose (D21), and at 4 weeks (D28) and 6 months (D180) after D0. Proteomic profiles at D0 and D28 were assessed with a multiplexed proximity extension assay (Olink) on plasma samples.ResultsAll HIV-infected patients mounted similar anti-SARS-CoV-2 humoral responses to those of HCs, albeit with lower titers of anti-trimeric S at D28 (P = .01). Only peripheral blood mononuclear cells of HIV-infected patients demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T-cell populations. Similar humoral titers were maintained between the 2 groups at 6-months follow-up. We additionally correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the 2 study groups.ConclusionsResponses of ART-treated HIV-infected patients, compared to those of HCs, were characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose, similarly to the HC schedule

STUDIO RETROSPETTIVO SULLA SICUREZZA ED EFFICACIA DELLA TERAPIA CON ANTICORPO MONOCLONALE RITUXIMAB IN PAZIENTI AFFETTI DA ARTRITE REUMATOIDE: ESPERIENZA REAL LIFE DELLA U.O. DI REUMATOLOGIA DI PISA

L'artrite reumatoide (AR) è una malattia infiammatoria sistemica cronica, caratterizzata da diverse manifestazioni cliniche ma il quadro tipico dell’AR è rappresentato da un processo infiammatorio sinoviale persistente che interessa prevalentemente le piccole e grandi articolazioni diartrodali, ad impronta destruente, spesso associata con la positività del fattore reumatoide (FR) . La prevalenza in Italia è nell'ordine 0,5 % con netta predilezione per il sesso femminile (rapporto uomini: donne di 1:3). La prevalenza aumenta con l’età e le differenze tra i due sessi diminuiscono nella popolazione più anziana. L’insorgenza è frequente tra la quarta e quinta decade; l’80% dei pazienti sviluppa la malattia in un’età compresa fra i 35 e i 50 anni. L'AR presenta un'espressività clinica polimorfa, in rapporto alla topografia, al grado di evoluzione dell'impegno articolare ed alla possibile presenza di manifestazioni extra-articolari. La remissione della sintomatologia, l’arresto dell’evoluzione del danno anatomico ed il recupero funzionale sono i principali obiettivi della terapia dell'AR. Il trattamento "sintomatico" si basa sull'impiego isolato o combinato degli antalgici puri (paracetamolo, trama¬dolo) e degli anti-infiammatori non steroidei (FANS) e steroidei. Il trattamento ''di fondo" dell'AR ha come finalità principale quella di indurre la remissione della flogosi e di arrestare l' evoluzione del danno anatomico: i farmaci utilizzati a tale scopo rientrano nel gruppo dei Disease Modifying Anti-Rheumatic Drug (DMARD) e comprendono un'ampia ed eterogenea gamma di molecole: idrossiclorochina, sulfasalazina, Sali d'oro, mtx, lfn, ciclosporina A, farmaci biologici,tra questi soggetto dello studio e l’anticorpo monoclonale Rituximab. Questo lavoro di tesi si basa sull’esperienza della U.O. di Reumatologia di Pisa valutando la sicurezza del farmaco tramite l’analisi degli eventi avversi e infettivi sviluppati dopo il trattamento, e l’efficacia in soggetti affetti da AR analizzando le differenze di vari gruppi: in base al sesso e all’età, in soggetti trattati in monoterapia vs terapia d’associazione, soggetti FR+ vs FR-, soggetti AntiCCP+ vs AntiCCP-

Effectiveness of palliative home-care services in reducing hospital admissions and determinants of hospitalization for terminally ill patients followed up by a palliative home-care team: A retrospective cohort study.

Abstract Background:It has been demonstrated that most patients in the terminal stages of cancer would benefit from palliative home-care services.Aim:The aim of this study was to assess the effectiveness of appropriate palliative home-care services in reducing hospital admissions, and to identify factors predicting the likelihood of patients treated at home being hospitalized.Design:Retrospective cohort study.Setting/participants:We enrolled all 402 patients listed by the Local Health Authority No. 5, Veneto Region (North-East Italy), as dying of cancer in 2011.Results:Of the cohort considered, 39.9% patients had been taken into care by a palliative home-care team. Irrespective of age, gender, and type of tumor, patients taken into care by the palliative home-care team were more likely to die at home, less likely to be hospitalized, and spent fewer days in hospital in the last 2 months of their life. Among the patients taken into care by the palliative home-care team, those with hematological cancers and hepatocellular carcinoma were more likely to be hospitalized, and certain symptoms (such as dyspnea and delirium) were predictive of hospitalization.Conclusions:Our study confirms the effectiveness of palliative home care in enabling patients to spend the final period of their lives at home. The services of a palliative home-care team reduced the consumption of hospital resources. This study also provided evidence of some types of cancer (e.g. hematological cancers and hepatocellular carcinoma) being more likely to require hospitalization, suggesting the need to reconsider the pathways of care for these diseases

Massive Cerebrospinal Fluid Leak of the Temporal Bone

Cerebrospinal fluid (CSF) leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS) with subsequent radiation treatment and second operation with total VS resection

Posterior reversible encephalopathy syndrome-Insight into pathogenesis, clinical variants and treatment approaches

Posterior reversible encephalopathy syndrome is a rare clinicoradiological entity characterized by typical MRI findings located in the occipital and parietal lobes, caused by subcortical vasogenic edema. It was first described as a distinctive syndrome by Hinchey in 1996. Etiopathogenesis is not clear, although it is known that it is an endotheliopathy of the posterior cerebral vasculature leading to failed cerebral autoregulation, posterior edema and encephalopathy. A possible pathological activation of the immune system has been recently hypothesized in its pathogenesis. At clinical onset, the most common manifestations are seizures, headache and visual changes. Besides, tinnitus and acute vertigo have been frequently reported. Symptoms can be reversible but cerebral hemorrhage or ischemia may occur. Diagnosis is based on magnetic resonance imaging, in the presence of acute development of clinical neurologic symptoms and signs and arterial hypertension and/or toxic associated conditions with possible endotheliotoxic effects. Mainstay on the treatment is removal of the underlying cause. Further investigation and developments in endothelial cell function and in neuroimaging of cerebral blood flow are needed and will help to increase our understanding of pathophysiology, possibly suggesting novel therapies